Challenges in conducting clinical trials in children: approaches for improving performance.
Challenges in conducting clinical trials in children: approaches for improving performance.
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DOI：
10.1586/ecp.09.40
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发表时间：
2009-11-01
影响因子：
4.4
通讯作者：
Kern, Steven E
中科院分区：
文献类型：
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作者：
Kern, Steven E
欧洲和美国最近的立法变化增加了药物开发人员的责任，有目的地研究他们在儿童中销售的药物，以便提出具体的剂量建议，以帮助临床医生使用。通常，临床医生使用药物或经验为基础的理由来选择用于儿童的剂量，通常以尝试在儿童中实现与成人相同的剂量暴露或药代动力学特征的方式。然而，在超说明书使用期间，可能无法系统地探索该方法是否达到必要的剂量暴露或所需的暴露效应。这为儿童，特别是非常年幼的儿童（即，小于2岁），其中发育期间的因素组合可影响药代动力学和药效学。在儿童中研究新的治疗剂的伦理，生理和统计差异提出了经济挑战，可能会产生意想不到的激励-积极和消极的-任何个人开发者谁试图满足新的立法要求，研究药物在儿童中。应该继续强调学术临床药理学项目的创造性方法和途径，以更好地了解儿童与成人的这些差异。使用从成人研究、临床前研究、具有相似化学或药理学的化合物研究或儿童与成人之间已知生理差异获得的知识信息的能力对于为儿童选择合适的剂量并实现这些监管目标至关重要。
Recent legislative changes in both Europe and the USA have increased the responsibility of drug developers to purposefully study the agents they market in children so that specific dosing recommendations can be made to assist clinicians in their use. Typically, clinicians use empiricalor experiential-based rationales for selecting the dose to use in children, generally in a manner that attempts to achieve the same dose-exposure or pharmacokinetic profile in children as in adults. However, whether this approach achieves the necessary dose exposure or exposure effect needed may not be systematically explored during off-label use. This creates the opportunity for under- or over-exposure in children, particularly in very young children (i.e., less than 2 years old) where a combination of factors during development can effect both pharmacokinetics and pharmacodynamics. The ethical, physiological and statistical differences of studying new therapeutic agents in children present economic challenges that may create unintended incentives - both positive and negative - for any individual developer who tries to meet the requirements of new legislation to study pharmaceutical agents in children. There should be a continued emphasis in academic clinical pharmacology programs towards creative methods and approaches to better understand these differences in children compared with adults. The ability to use information from knowledge obtained from adult studies, from preclinical studies, from studies of compounds with similar chemistry or pharmacology, or from known physiological differences between children and adults is essential to choosing a suitable dose for children and achieving these regulatory aims.